Genes, Journal Year: 2024, Volume and Issue: 15(6), P. 659 - 659
Published: May 22, 2024
Ageing has been identified as an independent risk factor for various diseases; however, the physiological basis and molecular changes related to ageing are still largely unknown. Here, we show that level of APPL2, adaptor protein, is significantly reduced in major organs aged mice. Knocking down APPL2 causes premature human umbilical vein endothelial cells (HUVECs). We find a lack
Language: Английский
Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 94, P. 102181 - 102181
Published: Jan. 4, 2024
Language: Английский
Citations
36
Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14
Published: Oct. 3, 2023
Experimental studies in animal models of aging such as nematodes, fruit flies or mice have observed that decreased levels insulin signaling promotes longevity. In humans, hyperinsulinemia and concomitant resistance are associated with an elevated risk age-related diseases suggestive a shortened healthspan. Age-related disorders include neurodegenerative diseases, hypertension, cardiovascular disease, type 2 diabetes. High ambient concentrations promote increased lipogenesis fat storage, heightened protein synthesis accumulation non-functional polypeptides due to limited turnover capacity. Moreover, there is impaired autophagy activity, less endothelial NO synthase activity. These changes mitochondrial dysfunction oxidative stress. The cellular stress induced by anabolic activity initiates adaptive response aiming at maintaining homeostasis, characterized activation the transcription factor Nrf2, AMP activated kinase, unfolded response. This protective more potent long-lived human species than short-lived research resulting stronger pro-aging impact nematodes flies. insulin-induced cell decreases age, because increase but Nrf2 activation. detrimental might be contained adopting lifestyle low insulin/insulin enhances stress, dietary restriction exercise.
Language: Английский
Citations
26
Current Sleep Medicine Reports, Journal Year: 2024, Volume and Issue: 10(1), P. 23 - 33
Published: Jan. 23, 2024
Abstract Purpose of Review The neuroendocrine stress response is a natural process our body which, however, might become toxic if not properly turned on and off. Resilience the ability to adapt adverse situations and, particularly, cope with uncontrolled stress. are two opposite faces same coin, both deeply linked sleep: low resilience means higher through that, more sleep disorders. aim present paper review complex relationship between these actors highlight possible positive role good in contrasting chronic situations. Recent Findings Promotion cognitive-behavioral therapy for insomnia patients improves quality produces lower general stress, depressive symptom severity, better global health. Summary Sleep modifiable behavior according recent studies, its improvement enhance turn, reduce
Language: Английский
Citations
11
Aging Cell, Journal Year: 2024, Volume and Issue: 23(10)
Published: July 2, 2024
Abstract The dynamicity of the mitochondrial network is crucial for meeting ever‐changing metabolic and energy needs cell. Mitochondrial fission promotes degradation distribution mitochondria, while fusion maintains function through complementation components. Previously, we have reported that networks are tubular, interconnected, well‐organized in young, healthy C. elegans , but become fragmented disorganized with advancing age models age‐associated neurodegenerative disease. In this work, examine effects increasing or capacity by ubiquitously overexpressing gene drp‐1 genes fzo‐1 eat‐3 individually combination. We then measured function, morphology, physiologic rates, stress resistance, lifespan. Surprisingly, found overexpression either machinery both resulted an increase fragmentation. Similarly, strains extended lifespans increased which case appears to be at least partially due upregulation multiple pathways cellular resilience these strains. Overall, our work demonstrates expression extends lifespan improves biological without promoting maintenance a youthful morphology. This highlights importance mitochondria longevity.
Language: Английский
Citations
9
bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown
Published: July 7, 2024
SUMMARY Health is strongly affected by aging and lifespan-modulating interventions, but the molecular mechanisms of mortality regulation remain unclear. Here, we conducted an RNA-seq analysis mice subjected to 20 compound treatments in Interventions Testing Program (ITP). By integrating it with data from over 4,000 rodent tissues representing responses genetic, pharmacological, dietary interventions established survival data, developed robust multi-tissue transcriptomic biomarkers mortality, capable quantifying change lifespan both short-lived long-lived models. These tools were further extended single-cell human demonstrating common across cell types species. Via a network analysis, identified annotated 26 co-regulated modules longevity tissues, interpretable module-specific clocks that capture aging- mortality-associated phenotypes functional components, including, among others, inflammatory response, mitochondrial function, lipid metabolism, extracellular matrix organization. captured characterized acceleration biological age induced progeria models chronic diseases rodents humans. They also revealed rejuvenation heterochronic parabiosis, early embryogenesis, cellular reprogramming, highlighting universal signatures shared age-related disease. included Cdkn1a Lgals3 , whose plasma levels demonstrated strong association all-cause disease incidence risk factors, such as obesity hypertension. Overall, this study uncovers hallmarks mammalian organs, types, species rejuvenation, exposing fundamental longevity.
Language: Английский
Citations
8
Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)
Published: Feb. 7, 2024
Abstract Magnolol is a naturally occurring polyphenolic compound in many edible plants, which has various biological effects including anti-aging and alleviating neurodegenerative diseases. However, the underlying mechanism on longevity uncertain. In this study, we investigated effect of magnolol lifespan Caenorhabditis elegans explored mechanism. The results showed that treatment significantly extended nematode alleviated senescence-related decline model. Meanwhile, enhanced stress resistance to heat shock, hydrogen peroxide (H 2 O ), mercuric potassium chloride (MeHgCl) paraquat (PQ) nematode. addition, reduced reactive oxygen species malondialdehyde (MDA) levels, increased superoxide dismutase catalase (CAT) activities nematodes. also up-regulated gene expression sod-3 , hsp16.2 ctl-3 daf-16 skn-1 hsf-1 sir2.1 etc., down-regulated daf-2 promoted intranuclear translocation lifespan-extending were reversed insulin/IGF signaling (IIS) pathway-related mutant lines, age-1 sir-2.1 suggesting IIS involved modulation by magnolol. Furthermore, improved age-related neurodegeneration PD AD C. models. These indicate may enhance health span through pathways. Thus, current findings implicate as potential candidate ameliorate symptoms aging.
Language: Английский
Citations
6
Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 161 - 161
Published: Jan. 10, 2025
The functionality of redox metabolism is frequently named as an important contributor to the processes aging and anti-aging. Excessive activation free radical reactions accompanied by inability antioxidant defense (AOD) mechanisms control flow reactive oxygen species (ROS) leads persistence oxidative stress, hypoxia, impaired mitochondrial energy function reduced ATP potential. From a long-term perspective, such changes contribute development chronic diseases facilitate aging. In turn, preconditioning biosystem with small doses stressful stimuli might cause mobilization AOD excessive ROS, which supports optimal functioning reactions. Those are crucial importance for anti-aging also known eustress or hormetic response. To ensure continuous support mild pro-oxidant activity in metabolic system, close monitoring timely corrections preventing ROS production required. paper introduces potential heart rate variability (HRV) biomarker functional reserves tool measure stress resilience during practical approaches interpretation HRV provided based on total power, power response orthostatic test activities all spectral components. It suggested that complex those parameters can reflect depth may be used guide lifestyle interventions promote active longevity.
Language: Английский
Citations
0
Published: Jan. 27, 2025
Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, healthspan by rewiring endogenous metabolism. However, there five FMOs mammalian FMOs, it is not known whether promoting health benefits role this gene family. Here, we report expression fmo-4 lifespan extension paraquat resistance downstream both dietary restriction inhibition mTOR. We find overexpression just the hypodermis sufficient for these benefits, significantly modifies transcriptome. By analyzing changes expression, genes related to calcium signaling altered expression. Highlighting importance homeostasis pathway, overexpressing animals sensitive thapsigargin, an ER stressor inhibits flux from cytosol lumen. This calcium/ interaction solidified data showing modulating intracellular with either small molecules or genetics can change and/or interact affect resistance. Further analysis pathway where modulates activating transcription factor-6 ( atf-6 ), whose knockdown induces requires Together, our identify as longevity-promoting actions pathways homeostasis.
Language: Английский
Citations
0
Advanced Science, Journal Year: 2025, Volume and Issue: unknown
Published: Jan. 31, 2025
Environmental factors are linked to aging and age-related diseases. Emerging evidence suggests that enhancing body's resistance xenobiotics might be an anti-aging strategy. The constitutive androstane receptor (CAR) regulates drug-metabolizing enzymes transporters, coordinating metabolism immune responses adapt stress triggered by exogenous exposure. However, the impact of activating CAR on remains unknown. In this study, Caenorhabditis elegans (C. elegans), drug-induced premature mice, senescence accelerated P8 (SAMP8) mice used as models explore effects activation lifespan healthspan, along with underlying mechanisms. results showed hCAR agonist CITCO mCAR TCPOBOP prolonged healthspan in model organism. longevity were attenuated homozygous nhr-8/daf-12 mutant C. well CAR-/- mice. elegans, activated both anti-stress detoxification genes, increased environmental adversities. Additionally, lifespan-extending xenobiotic resistant related regulation pathways. Furthermore, improved neurodegeneration models. Taken together, suggest agonists may enhancement animals.
Language: Английский
Citations
0
eLife, Journal Year: 2025, Volume and Issue: 13
Published: Feb. 14, 2025
Flavin-containing monooxygenases (FMOs) are a conserved family of xenobiotic enzymes upregulated in multiple longevity interventions, including nematode and mouse models. Previous work supports that C. elegans fmo-2 promotes longevity, stress resistance, healthspan by rewiring endogenous metabolism. However, there five FMOs mammalian FMOs, it is not known whether promoting health benefits role this gene family. Here, we report expression fmo-4 lifespan extension paraquat resistance downstream both dietary restriction inhibition mTOR. We find overexpression just the hypodermis sufficient for these benefits, significantly modifies transcriptome. By analyzing changes expression, genes related to calcium signaling altered expression. Highlighting importance homeostasis pathway, overexpressing animals sensitive thapsigargin, an ER stressor inhibits flux from cytosol lumen. This calcium/ interaction solidified data showing modulating intracellular with either small molecules or genetics can change and/or interact affect resistance. Further analysis pathway where modulates activating transcription factor-6 ( atf-6 ), whose knockdown induces requires Together, our identify as longevity-promoting actions pathways homeostasis.
Language: Английский
Citations
0